IGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels

Figure 1

IGF-1 treatment reactivates plasticity in the adult visual cortex and decreases intracortical GABA levels. (a) An OD shift in favor of the open eye was evident in IGF-1-infused rats (IGF-1+MD; 𝑛=5, C/I VEP ratio = 1.2 ± 0.17) with respect to adult animals with binocular vision (Nor+Bin; 𝑛=5, C/I VEP ratio = 2.42 ± 0.16, one-way ANOVA 𝑃=0.0002, post hoc Holm Sidak method, 𝑃<0.05). No modification of the C/I VEP ratio was detected in either saline-treated animals (SAL+MD; 𝑛=5, C/I VEP ratio = 2.67 ± 0.15, One-way ANOVA, post hoc Holm Sidak method) or normal adult rats (Nor+MD; 𝑛=7, C/I VEP ratio = 2.53 ± 0.25, One-way ANOVA, post hoc Holm Sidak method). IGF-1 treated rats with binocular vision (IGF-1+Bin; 𝑛=3) exhibited a C/I VEP ratio (2.37 ± 0.12) completely comparable to that of untreated Nor+Bin animals (One-way ANOVA, post hoc Holm Sidak method). Insert: the change of OD in IGF-1-treated rats was due to a decrease of the deprived eye (contra) strength. The amplitude of VEPs recorded in response to the stimulation of the occluded eye in IGF-1+MD rats (0.35 ± 0.05) was significantly lower with respect to that obtained in saline-treated animals following MD (0.68 ± 0.12; t-test; 𝑃=0.047). No difference was detected in VEP amplitudes recorded after the stimulation of the open (Ipsi) eye (IGF-1+MD: 0.38 ± 0.11; SAL+MD: 0.32 ± 0.05; t-test; 𝑃=0.627). VEP amplitudes at the recording site in the VC contralateral to the occlusion were normalized to the sum of the response to stimulation of the contralateral and ipsilateral eye, as described previously [10–12]. (b) Full rescue of VA was evident in reverse-sutured IGF-1 treated rats (IGF-1+RS, 𝑛=5): VA of the long-term deprived eye (0.93 ± 0.06 cycles per degree, c/deg) was not different from that of the fellow eye (0.94 ± 0.04 c/deg; paired t-test, 𝑃=0.837). No sign of recovery was detected either in reverse-sutured animals infused with saline (SAL+RS, 𝑛=5; VA for the long-term deprived eye = 0.72±0.03 c/deg; VA for the open eye 0.96 ± 0.01 c/deg; paired t-test, 𝑃<0.001) or in reverse-sutured normal rats (Nor+RS, n = 5; VA for the long-term deprived eye = 0.67 ± 0.01 c/deg; VA for the open eye 1.03 ± 0.03 c/deg; paired t-test; P < 0.001) Insert, while in Nor-RS rats (C/I VEP ratio = 1.02 ± 0.08) there was no recovery of binocularity (One-way ANOVA, post hoc Holm Sidak method); in IGF1+RS the C/I VEP ratio is in the range of normal adult values (C/I VEP ratio 2.12 ± 0.13, One-way ANOVA, 𝐹_(3-16) = 40.24, 𝑃<0.0001, post hoc Holm Sidak method). No recovery of OD was detected in SAL+RS animals (𝑛=5; C/I VEP ratio = 0.86 ± 0.11; One-way ANOVA, post hoc Holm Sidak method). (c) Extracellular GABA levels were significantly lower in the VC of IGF-1-treated rats (IGF-1; 𝑛=6; 0.87 ± 0.17 μM) with respect to saline-treated (SAL; 𝑛=5; 4.46 ± 0.17 μM) and untreated animals (Nor; 𝑛=8,4.62±0.97 μM; One-way ANOVA, 𝐹_(2-16) = 7.445, 𝑃=0.0052, post hoc Tukey test, 𝑃<0.05). (d) No change in glutamate (GLU) levels between IGF-1-treated (3.88 ± 0.4 μM) and control groups (SAL: 4.48 ± 0.6 μM; Nor: 3.74 ± 0.3 μM) was detected (One-way ANOVA, 𝐹_(2-15) = 0.744, 𝑃=0.491). The grey box denotes the C/I VEP ratio range in adult normal animals. *Statistical significance. Error bars indicate SEM.

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